Bartosiewicz M J, Jenkins D, Penn S, Emery J, Buckpitt A
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
J Pharmacol Exp Ther. 2001 Jun;297(3):895-905.
DNA arrays containing 260 unique genes involved in phase I and II metabolism, heat shock, DNA repair, inflammation, transcription, and housekeeping were used to examine gene expression patterns in liver and kidney in response to five classes of chemicals (polyaromatic hydrocarbons: benzo(a)pyrene, 3-methylcholanthrene; DNA alkylators: dimethylnitrosamine, ethylnitrosourea; peroxisome proliferators: diethylhexylphthalate, clofibrate; heavy metals: CdCl(2), HgCl(2); and oxidative stressors: CCl(4), bromobenzene). Time course experiments in mice were carried out in both tissues for each chemical and dose-response studies were used to further evaluate several of these chemicals. Each pair of chemicals yielded a similar pattern of gene expression distinct from the other four classes of chemicals. Both peroxisome proliferators up-regulated Cyp4a10, acyl-CoA thioesterase, and insulin-like growth factor binding protein-1, whereas the DNA alkylators altered the expression of monokine induced by gamma-interferon, the metallothioneins, p21, and several acute phase proteins. For each of the five classes of chemicals tested, several genes that were induced or repressed were common in each chemical exposure, whereas other genes were unique for that specific class of compound. Both time and dose are important factors in differentiating between chemical classes. Likewise, comparison of changes in messenger RNA expression between the kidney and liver of treated animals indicates that gene arrays may be useful in determining the comparative toxicity of chemicals in various tissues but that exposure to uncharacterized chemicals will have to be monitored in several tissues.
含有参与I期和II期代谢、热休克、DNA修复、炎症、转录及管家功能的260个独特基因的DNA阵列，被用于检测肝脏和肾脏中基因表达模式对五类化学物质（多环芳烃：苯并(a)芘、3-甲基胆蒽；DNA烷化剂：二甲基亚硝胺、乙基亚硝基脲；过氧化物酶体增殖剂：邻苯二甲酸二乙基己酯、氯贝丁酯；重金属：氯化镉、氯化汞；以及氧化应激剂：四氯化碳、溴苯）的响应。在小鼠体内对每种化学物质进行了两个组织的时间进程实验，并通过剂量反应研究进一步评估其中几种化学物质。每对化学物质产生的基因表达模式相似，与其他四类化学物质不同。两种过氧化物酶体增殖剂均上调了Cyp4a10、酰基辅酶A硫酯酶和胰岛素样生长因子结合蛋白-1，而DNA烷化剂改变了γ-干扰素诱导的单核因子、金属硫蛋白、p21和几种急性期蛋白的表达。对于所测试的五类化学物质中的每一类，在每次化学物质暴露中，有几个基因被诱导或抑制是共同的，而其他基因则是该特定类化合物所特有的。时间和剂量都是区分化学物质类别的重要因素。同样，比较处理动物肾脏和肝脏中信使RNA表达的变化表明，基因阵列可能有助于确定化学物质在各种组织中的相对毒性，但必须在多个组织中监测对未表征化学物质的暴露情况。
